Grignard addition-reactions to glycosulose derivatives

The course of Grignard addition-reactions to 1,2:5,6-di-O-isopropylidene-α-D-ribo-hexofuranos-3-ulose (1) has been examined as a function of the nature of the reagent, the solvent, the halide, and the temperature. Ethylmagnesium bromide in ether at — 14° converted 1 into 60% of the 3-C-ethyl-D-allo adduct 2. The latter was convertible in 90% yield into the 3-benzyl ether 6, despite the tertiary nature of the hydroxyl group. The use of tetrahydrofuran (THF) or THF-ether at higher temperatures, or of ethylmagnesium iodide, lowered the yield of 2 and gave substantial proportions of such side products as 1,2:5,6-di-O-isopropylidene-α-D-allofuranose (3). 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (4), and the hydrate (5) of the starting ketone 1. Phenylmagnesium bromide in ether or THF converted 1 into the 3-C-phenyl-D-allo derivative 7 in 84% yield, accompanied by only minor proportions of side products; the latter were the 3-C-phenyl-D-gluco adduct 8 and the product (9) of 5,6-dioxolane ring-opening. The structures of 8 and 9 were confirmed by an acetylation-deacetylation sequence, and by n.m.r. spectroscopy. The 3-C-phenyl-D- allo derivative 7 could be converted in 95% yield into its 3-benzyl ether 10. Cyclohexylmagnesium bromide reacted with 1 in ether or THF at various temperatures to give 3-C-cyclohexyl-1,2:5,6-di-O-isopropylidene-α-D)-allofuranose (11) in low yields; the main product generally encountered was 3. with variable proportions of 4, 1,2-O-isopropylidene-α-D-allofuranose (18), the hydrate 5, and a dimeric product 19 (further characterized as its oxime 20). Compound 11 was, however, obtainable in >95% yield by reducing 7 with hydrogen in the presence of rhodium-on-alumina. Phenylmagnesium bromide reacted with the 4-ketone derivative 25 in THF at 0° to give 83% of 1,6-anhydro-2,3-O-isopropylidene-3-C-phenyl-β-D-talopyranose (26), and no side-products were detected.